TZD18 enhances growth inhibition of imatinib. (A) Cells (2 × 105/mL) were incubated with different concentrations of imatinib, as indicated in the figure, in the presence or absence of TZD18 (10 μM, 4 days). Cell proliferation was measured by the MTT assay, as described in “Materials and methods.” Results are expressed as proliferation percentage of control (without treatment). Values are mean ± SD of 6 parallel experiments. (B) Statistical analysis of the effects of the combination of TZD18 and imatinib. BV173, SD1, and Sup B-15 cells were cultured in the presence of escalating doses of imatinib (0.25, 0.5, 1, 2.5 μM) or TZD18 (5, 10, 15, 20 μM) and the combination of 0.5 μM imatinib with varied concentrations of TZD18 (5, 10, 15, 20 μM) or the combination of 10 μM TZD18 with varied concentrations of imatinib (0.25, 0.5, 1, 2.5 μM). After 4 days, cell proliferation was measured with MTT assay. CI values for each data point of this nonconstant ratio design were calculated using Calcusyn software. All CI values were less than 1. Representative diagnosis-normalized isobolograms obtained from SD1 cells are shown (top, TZD18 concentration fixed at 10 μM; bottom, imatinib concentration fixed at 0.5 μM).
